Development of freeze-dried kit for the preparation of [۹۹mTc]Tc-HYNIC-ALUG: A potential agent for imaging of prostate specific membrane antigen

Introduction: Prostate-specific membrane antigen (PSMA) is increasingly recognized as a viable target for imaging and therapy of Prostate cancer (PCa). In this study, we introduce the freeze-dried kit formulation of [۹۹mTc]Tc-HYNICALUG for easy clinical evaluation of prostate cancer.Methods: In this work, an in silico modeling of the urea-based PSMA small molecule (HYNIC-ALUG) was performed to check its interaction with human glutamate carboxypeptidase II and compared it with experimental results. The HYNIC-PSMA kit was formulated for easy preparation of [۹۹mTc]Tc-HYNIC-ALUG. The kit contained a freeze-dried mixture of HYNIC-ALUG, coligands SnCl۲.۲H۲O, and antioxidant D-mannitol.Results: The calculated Ki value (inhibition/dissociation constant) was ۴.۵۵ which showed excellent binding affinity of HYNIC-ALUG with PSMA.  miLogP and cLogS values are -۴.۰۴ and -۳.۰۷ respectively showing its hydrophilic character and predicting its excellent distribution in biological fluids.  Subsequently, the radiochemical purity of the HYNIC-PSMA kit was ۹۹.۱ ± ۱.۳۲% (n = ۶) determined by radio-ITLC and by HPLC as well. In vitro stability in saline and serum was studied up to ۴ h and showed high stability (≥ ۹۶%). The distribution of [۹۹mTc]Tc-HYNIC-ALUG was carried out in two patients and SPECT/CT planar images were acquired at ۲h and ۴h respectively. Bio-physiological distribution of [۹۹mTc]Tc-HYNIC-ALUG was observed normally in lacrimal, salivary glands, liver, spleen, gut, kidneys, and urinary bladder.Conclusion: The HYNIC-ALUG freeze-dried kit could be used for easy preparation of [۹۹mTc]Tc-HYNIC-ALUG and can be considered as a potential agent for the diagnosis, staging, and restaging of advanced prostate cancer.

کلیدواژه ها:

prostate cancer ، Technetium-۹۹m ، HYNIC-ALUG ، SPECT imaging ، Clinical evaluation